Conotoxin
File:Ziconotide 1DW5.png
Schematic diagram of the three-dimensional structure of ω-conotoxin MVIIA (ziconotide). Disulfide bonds are shown in gold.
A conotoxin is one of a group of neurotoxic peptides isolated from the venom of the marine cone snail, genus Conus.
Conotoxins, which are peptides consisting of 10 to 30 amino acid residues, typically have one or more disulfide bonds. Conotoxins have a variety of mechanisms of actions, most of which have not been determined. However it appears that many of these peptides modulate the activity of ion channels.[1]
The number of conotoxins whose activities have been determined so far is five, and they are called the α(alpha)-, δ(delta)-, κ(kappa)-, μ(mu)-, and ω(omega)- types. Each of the five types of conotoxins attacks a different target:
- α-conotoxin inhibits acetylcholine receptors at nerves and muscles.[2]
- δ-conotoxin inhibits the inactivation of voltage-dependent sodium channels.[3]
- κ-conotoxin inhibits potassium channels.[4]
- μ-conotoxin inhibits voltage-dependent sodium channels in muscles.[5]
- ω-conotoxin inhibits N-type voltage-dependent calcium channels.[6] Because N-type voltage-dependent calcium channels are related to algesia (sensitivity to pain) in the nervous system, ω-conotoxin has an analgesic effect: the effect of ω-conotoxin M VII A is 100 to 1000 times that of morphine.[7] Therefore a synthetic version of ω-conotoxin M VII A has found application as an analgesic drug ziconotide (Prialt®).[8]
References
- ↑ Terlau H, Olivera BM (2004). "Conus venoms: a rich source of novel ion channel-targeted peptides". Physiol. Rev. 84 (1): 41–68. doi:10.1152/physrev.00020.2003. PMID 14715910.
- ↑ Nicke A, Wonnacott S, Lewis RJ (2004). "Alpha-conotoxins as tools for the elucidation of structure and function of neuronal nicotinic acetylcholine receptor subtypes". Eur. J. Biochem. 271 (12): 2305–19. doi:10.1111/j.1432-1033.2004.04145.x. PMID 15182346.
- ↑ Leipold E, Hansel A, Olivera BM, Terlau H, Heinemann SH (2005). "Molecular interaction of delta-conotoxins with voltage-gated sodium channels". FEBS Lett. 579 (18): 3881–4. doi:10.1016/j.febslet.2005.05.077. PMID 15990094.
- ↑ Shon KJ, Stocker M, Terlau H, Stühmer W, Jacobsen R, Walker C, Grilley M, Watkins M, Hillyard DR, Gray WR, Olivera BM (1998). "kappa-Conotoxin PVIIA is a peptide inhibiting the shaker K+ channel". J. Biol. Chem. 273 (1): 33–8. doi:10.1074/jbc.273.1.33. PMID 9417043.
- ↑ Li RA, Tomaselli GF (2004). "Using the deadly mu-conotoxins as probes of voltage-gated sodium channels". Toxicon 44 (2): 117–22. doi:10.1016/j.toxicon.2004.03.028. PMID 15246758.
- ↑ Nielsen KJ, Schroeder T, Lewis R (2000). "Structure-activity relationships of omega-conotoxins at N-type voltage-sensitive calcium channels". J. Mol. Recognit. 13 (2): 55–70. PMID 10822250.
- ↑ Bowersox SS, Luther R (1998). "Pharmacotherapeutic potential of omega-conotoxin MVIIA (SNX-111), an N-type neuronal calcium channel blocker found in the venom of Conus magus". Toxicon 36 (11): 1651–8. doi:10.1016/S0041-0101(98)00158-5. PMID 9792182.
- ↑ Prommer E (2006). "Ziconotide: a new option for refractory pain". Drugs Today 42 (6): 369–78. doi:10.1358/dot.2006.42.6.973534. PMID 16845440.
See also
External links
Protein tertiary structure | |
|---|---|
| General | Structural domain | Protein folding | Structure determination methods |
| All-α folds: | Helix bundle | Globin fold | Homeodomain fold | Alpha solenoid |
| All-β folds: | Immunoglobulin fold | Beta barrel | Beta-propeller |
| α/β folds: | TIM barrel | Leucine-rich repeat | Flavodoxin fold | Rossmann fold | Thioredoxin fold | Trefoil knot fold |
| α+β folds: | DNA clamp | Ferredoxin fold | Ribonuclease A | SH2-like fold |
| Irregular folds: | Conotoxin |
Navigation WikiDoc | WikiPatient | Popular pages | Recently Edited Pages | Recently Added
Pictures
There is no pharmaceutical or device industry support for this site and we need your viewer supported Donations | Editorial Board | Governance | Licensing | Disclaimers | Avoid Plagiarism | Policies
Table of Contents In Alphabetical Order | By Individual Diseases | Signs and Symptoms | Physical Examination | Lab Tests | Drugs
Editor Tools Become an Editor | Editors Help Menu | Create a Page | Edit a Page | Upload a Picture or File | Printable version | Permanent link | Maintain Pages | What Pages Link HereThere is no pharmaceutical or device industry support for this site and we need your viewer supported Donations | Editorial Board | Governance | Licensing | Disclaimers | Avoid Plagiarism | Policies
